Modulating effect of inositol hexaphosphate on arachidonic acid-dependent pathways in colon cancer cells

Prostaglandins Other Lipid Mediat. 2017 Jul:131:41-48. doi: 10.1016/j.prostaglandins.2017.08.002. Epub 2017 Aug 8.

Abstract

Cyclooxygenase (COX) and lipoxygenase (LOX) are key enzymes of arachidonic acid metabolism. Their products, prostaglandins and leukotrienes, are involved in the pathogenesis of inflammatory bowel diseases and colorectal cancer. The aim of the study was to examine the influence of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the expression of genes encoding COX and LOX isoforms and synthesis of their products (PGE2 and LTB4) in colon cancer cell line Caco-2 stimulated with pro-inflammatory agents (IL-1β/TNFα). Real-time RT-qPCR was used to validate mRNAs level of examined genes. The concentrations of COX-2 and 5-LOX proteins as well as PGE2 and LTB4 were determined by the ELISA method. Based on these studies it may be concluded that IP6 may limit inflammatory events in the colonic epithelium and prevent colon carcinomas by modulating the expression of genes encoding COX and LOX isoforms at both mRNA and protein levels as well as by affecting the synthesis and secretion of prostaglandins and leukotrienes.

Keywords: Colon cancer; Cyclooxygenase; IP6; Leukotriene B4; Lipoxygenase; Prostaglandin E2.

MeSH terms

  • Arachidonic Acid / metabolism*
  • Caco-2 Cells
  • Colonic Neoplasms / pathology*
  • Dinoprostone / biosynthesis
  • Dinoprostone / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Leukotriene B4 / biosynthesis
  • Leukotriene B4 / metabolism
  • Lipoxygenases / genetics
  • Phytic Acid / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects

Substances

  • RNA, Messenger
  • Leukotriene B4
  • Arachidonic Acid
  • Phytic Acid
  • Lipoxygenases
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone